iPS-Derived Early Oligodendrocyte Progenitor Cells from SPMS Patients Reveal Deficient In Vitro Cell Migration Stimulation

Cells. 2020 Jul 29;9(8):1803. doi: 10.3390/cells9081803.


The most challenging aspect of secondary progressive multiple sclerosis (SPMS) is the lack of efficient regenerative response for remyelination, which is carried out by the endogenous population of adult oligoprogenitor cells (OPCs) after proper activation. OPCs must proliferate and migrate to the lesion and then differentiate into mature oligodendrocytes. To investigate the OPC cellular component in SPMS, we developed induced pluripotent stem cells (iPSCs) from SPMS-affected donors and age-matched controls (CT). We confirmed their efficient and similar OPC differentiation capacity, although we reported SPMS-OPCs were transcriptionally distinguishable from their CT counterparts. Analysis of OPC-generated conditioned media (CM) also evinced differences in protein secretion. We further confirmed SPMS-OPC CM presented a deficient capacity to stimulate OPC in vitro migration that can be compensated by exogenous addition of specific components. Our results provide an SPMS-OPC cellular model and encouraging venues to study potential cell communication deficiencies in the progressive form of multiple sclerosis (MS) for future treatment strategies.

Keywords: cell migration; disease modeling; iPSCs; oligodendrocyte progenitor cells (OPCs); secondary progressive multiple sclerosis (SPMS); secretome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Cell Communication / genetics
  • Cell Differentiation / genetics
  • Cell Movement / genetics*
  • Culture Media, Conditioned / analysis
  • Culture Media, Conditioned / metabolism
  • Female
  • Gene Expression Profiling / methods
  • HEK293 Cells
  • Humans
  • Induced Pluripotent Stem Cells / metabolism*
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Multiple Sclerosis, Chronic Progressive / metabolism*
  • Multiple Sclerosis, Chronic Progressive / pathology
  • Oligodendrocyte Precursor Cells / metabolism*
  • Proteome*
  • Proteomics / methods
  • Transcriptome
  • Transfection


  • Culture Media, Conditioned
  • Proteome